Effect of resuscitation on glucose-6-phosphatase gene expression following hemorrhagic shock

Glucose-6-phosphatase (Glu-6-pase) is a key enzyme in the homeostatic regulation of blood glucose concentration. Recent data from our laboratory indicate that hemorrhagic shock (HS) acutely affects Glu-6-pase activity, and points to a mechanism involving hormone induction of Glu-6-Pase mRNA. In the present study we address the molecular mechanisms that bring about the alteration in glucose metabolism during HS and fluid resuscitation. HS was induced in fasted anesthetized rats by reduction of blood pressure to 40mm Hg and maintaining in shock for 30 minutes, by withdraw or infusion of shed blood. The rats in the control group were anesthetized and carmulated and observed for 30 minutes. A third group of rats underwent induction and maintenance of HS for 30 minutes followed by resuscitation to a mean asterial pressure greater than 90mm HG by infusion of lactated Ringers solution (LR). The rat livers were then freeze clamped in liquid nitrogen and stored at -70°C. After 30 minutes of HS, mRNA levels for p-enolpyruvate carboxykinase (PEPCK) and fructose-1,6-bisphosphatase were similar to those of controlled rats but significantly lower mRNA values for 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (6PF2K/FBPase) and higher values of Glu-6-pase mRNA were observed. LR resuscitation was associated with a further increase in Glu-6-Pase and 6PF2K/FBPase gene expression. These results indicate that LR resuscitation alone is not effective in returning Glu-6-Pase and 6PF2K/FBPase gene expression to pre-shock levels.